Radiometal-Labeled Photoactivatable Pt(IV) Anticancer Complex for Theranostic Phototherapy.

A novel photoactivatable Pt(IV) diazido anticancer agent, Pt-succ-DFO, bearing a pendant deferoxamine (DFO) siderophore for radiometal chelation, has been synthesized for the study of its in vivo behavior with radionuclide imaging. Pt-succ-DFO complexation of Fe(III) and Ga(III) ions yielded new heterobimetallic complexes that maintain the photoactivation properties and photocytotoxicity of the parent Pt complex in human cancer cell lines. Radiolabeled Pt-succ-DFO-68Ga (t1/2 = 68 min, positron emitter) was readily prepared under mild conditions and was stable in the dark upon incubation with human serum. PET imaging of Pt-succ-DFO-68Ga in healthy mice revealed a promising biodistribution profile with rapid renal excretion and limited organ accumulation, implying that little off-target uptake is expected for this class of agents. Overall, this research provides the first in vivo imaging study of the whole-body distribution of a photoactivatable Pt(IV) azido anticancer complex and illustrates the potential of radionuclide imaging as a tool for the preclinical development of novel light-activated agents.

Computed Tomography of Cartilage: An Exploration of Novel Cationic Bismuth Contrast Agent.

Accurate diagnosis of minor cartilage injuries with delayed contrast-enhanced computed tomography (CECT) is challenging as poor diffusion and toxicity issues limit the usage of common CT contrast agents. Hence, the design of safe contrast agents with physiochemical properties suitable for fast, deep cartilage imaging is imminent. Herein, a novel cationic bismuth contrast agent (Bi-DOTAPXD) based on dodecane tetraacetic acid (DOTA) was synthesized and examined for CECT of cartilage. The complex was designed to improve diagnosis by utilising a net-positive charge for enhanced permeability through cartilage, inherent low-toxicity and high X-ray attenuation of bismuth. Osteochondral plugs (n = 12), excised from visually intact porcine articular cartilage were immersed in Bi-DOTAPXD (8 mg/mL) and Gd-DOTAPXD (10 mg/mL) contrast agents and scanned with a high-resolution microcomputed tomography scanner at multiple time-points. The mean Bi-DOTAPXD and Gd-DOTAPXD partitions at 45-min time-point were 85.7 ± 35.1 and 69.8 ± 30.2%, and the partitions correlated with the histopathological analysis of cartilage proteoglycan (PG) content (r) at 0.657 and 0.632, respectively. The time diffusion constants (τ) for Bi-DOTAPXD and Gd-DOTA were 121 and 159 min, respectively. Diffusion Bi-DOTAPXD and Gd-DOTAPXD reflected inter-sample variation in cartilage PG content. Cationic Bi-DOTAPXD may have the potential as a CT agent for the diagnosis of cartilage.